1. Field of the Invention
The present invention is directed to active microfluidic devices.
2. Background Art
Microfluidic devices are miniature devices generally containing a plurality of interconnected microchannels, reservoirs, etc., of very small size. Microchannels may commonly have width and height dimensions of 10 μm to 300 μm, for example, although smaller and larger dimensions are possible as well. As an aim to miniaturization and cost reduction, it is desirable to construct “lab on a chip” devices which contain all necessary functions with the exception of external fluid supply, and electrical, magnetic, or pneumatic energy supply when appropriate.
Examples of microfluidic devices include micro flow cytometers as disclosed in K. Kurabayashi, et al., “Flow Cytometers and Detection System of Lesser Size,” published PCT Application No. WO 03/008937 A2 and motile sperm sorters as disclosed in S. Takayama, et al., “Process for Sorting Motile Particles from Lesser-Motile Particles and Apparatus Suitable Therefor,” filed Feb. 27, 2003 under Ser. No. 10/375,373, in the United States Patent and Trademark Office. However, numerous other microfluidic devices are disclosed in the literature, and increasing numbers of different applications are proposed, including chemical microreactors, micro carburetors, micro spectrophotometers, and devices for cell sorting, cell growth, etc. A novel, constant flow gravity driven pumping system is disclosed in S. Takayama et al., “Microfluidic Gravity Flow Pump with Constant Flow Rate,” published PCT Application No. WO 03/008102 A1, filed Jul. 18, 2002 under Ser. No. 10/198,477, in the United States Patent and Trademark Office.
In simple devices, flow of gas or liquid through the various flow channels may be initiated and controlled by external devices such as syringes, pipets, micropumps, etc. However, increasing complexity of such devices, the need to pump fluids “on chip,” the need to stop, start, or regulate flow, and the need to vary interchannel connectivity has created the desire to incorporate active devices “on chip.” Unfortunately, prior attempts to incorporate active valves and pumps have created enormous difficulties with respect to device fabrication, and have often required that the active devices be connected with macroscopic energizing auxiliaries such as pneumatic supply tubing, etc.
For example, the Quake group has disclosed integrated microfluidic systems such as cell sorters with an array of over 2000 individually addressable fluid reservoirs. However, while the number of channels is not limited, the number of individually actuated components is limited due to the need to connect each pneumatic control channel to macroscopic air supply tubes. To compensate, a complex cluster activation scheme has been proposed. However, this scheme is incapable of individually addressing control sites. Moreover, such devices are difficult to fabricate. See, e.g., SCIENCE, January 2002, 295, pp. 647-651, Thorsen et al, Microfluidic Large-Scale Integration, SCIENCE, October 2002, 298, pp. 580-584, and MEMS, June 2000, 9, pp. 190-197. These devices are complex and costly to fabricate.
Peristaltic pneumatic pumps have been disclosed by M. A. Unger et al., SCIENCE 2000, 288, p. 113, in which successive pneumatic passageways cross a microchannel at right angles, and pump fluid through the microchannel by successive application. Once again, a macroscopic energy supply is required, and the device quickly becomes complex when multiple pumps and/or multiple channels are required.
It is well known that certain types of cell cultures, embryo growth, etc. require a changing environment. This changing environment mimics in vivo culture, and may include changing the concentrations of nutrients, growth factors, vitamins, etc., changing pH, presence or absence of growth inhibitors, etc. The changing environment may also be a change in flow rate of fluid or a periodic fluctuation of fluid flow. Changing such factors is typically quite complex.